Causes of male infertility are wide-ranging, and many cases are involved with various factors associated in a complex manner. Generally, spermatogenic dysfunction, obstruction of sperm transport, sperm dysfunction and sexual dysfunction are thought to be the four major reasons of male infertility. Among them, in spermatogenic dysfunction and sperm dysfunction, there exists oligozoospermia and asthenospermia exhibiting symptoms wherein sperm motility is lowered, or wherein sperm concentration or number of sperms is decreased. Further, unexplained sudden spermatogenic dysfunction is observed frequently as male infertility.
Sexual dysfunction is so-called erectile dysfunction, and it is reported to represent 15% of male infertility. Erection is attained when smooth muscle of corpus cavernosum penis is relaxed, blood flow from deep artery of penis is increased, and vein is compressed by the expansion of tissues at the same time, and thus blood flow is restricted. First, nitric oxide synthesized by nitric oxide (NO) synthetase in endothelia cells is diffused in smooth muscle cells in the corpus cavernosum penis. Next, NO binds with the heme of guanylate cyclase to activate the enzyme, and cyclic guanosine monophosphate (cGMP) is synthesized from guanosine triphosphate. As cGMP decreases calcium concentration in smooth muscle cells, relaxation of smooth muscles progresses with the increase of cGMP concentration, and the blood flow of penile artery increases.
Conventionally, hormone treatment and nonendocrine treatment were performed as treatment of male infertility. Specific examples include administration of hormonal agent such asgonadotropin and estrogen; and administration of nonendocrine agents including protease, adenosine 5′-triphosphate (ATP), coenzyme Q10, vitamins such as vitamin B12 and folic acid, antioxidant agents such as vitamin E and vitamin C, trace elements such as zinc and selenium, L-carnitine and herbal medicine. However, since these agents do not act specifically on germ cells or germ tissues, it cannot be said that they exert a significant effect.
Further, sildenafil citrate (hereinafter abbreviated as “sildenafil”) (see patent document 1) is manufactured and authorized by FDA as an agent for treating erectile dysfunction. Sildenafil exhibits an effect by inhibiting selectively an enzyme that metabolizes cGMP to non-activated 5′-cGMP.
However, it had drawbacks in that it is possible to induce rapid and significant decrease of blood pressure, or to induce angina impairing oxygen supply to heart as side effects. Moreover, it is said that the effectiveness is as low as about 50%.